The transplantation of major categories of central nervous system (CNS) cells (i.e. neurons, astrocytes) or CNS tissue fragments offers opportunities to study the developmental biology and immunological properties of these cells, to create animal models of CNS diseases such as Alzheimer's disease and to develop alternative strategies for the treatment of relentlessly progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and hereditary ataxia as well as to study other diseases, conditions and disorders characterized by loss, damage or dysfunction of neurons including transplantation of neuron cells into individuals to treat individuals suspected of suffering from such diseases, conditions and disorders. Indeed, recent pioneering efforts to utilize human fetal mesencephalic tissue grafts to ameliorate the extrapyramidal manifestations of drug induced and idiopathic Parkinson's disease emphasize the potential of transplanted human CNS tissues for the treatment of human neurodegenerative diseases (Freed, C. A., et al. 1992 New Engl. J. Med. 327:1549-1555; Spencer, D. D. et al. 1992 New Engl. J. Med. 327:1541-1548; and Widner, H., et al. 1992 New Engl. J. Med. 327:1556-1563). However, the results of these efforts have not been completely satisfactory.
The immortalization of CNS progenitor cells using constructs containing temperature sensitive promoters has enabled transplantation of genetically engineered precursors of neurons and glia, but brain grafts of these progenitors have given rise to mixed populations of glial and neuronal progeny (Cattaneo, E., and R. McKay 1991 TINS 14:338–340; Renfranz, P. J., et al. 1991 Cell 66:713–729; Snyder, E. Y., et al. 1992 Cell 68:33–51). An alternative strategy has been to use neuron-like transformed cell lines obtained from tumors of the CNS, but neoplastic neuron-like cells usually cannot be induced to permanently exit the cell cycle or they develop into tumors when transplanted into the rodent brain (Fung, K.-F. et al. 1992 J. Histochem. Cytochem. 40:1319–1328; Trojanowski, J. Q., et al. 1992 Molec. Chem. Neuropathol. 17:121–135; and Wiestler, O. D. et al. 1992 Brain Pathol. 2:47–59). A slowly dividing human neuronal cell line obtained from a child with unilateral megalencephaly was shown to exhibit a neuron-like phenotype in culture but grafts of these cells in the rodent CNS showed a mixture of neuronal and mesenchymal phenotypic properties (Poltorak, M., et al. 1992 Cell Transplant I:3–15).
There is a need for a method of generating animal models of CNS diseases and disorders by transplanting neurons into the brains of such animals to produce conditions which resemble or mimic CNS diseases, conditions or disorders.
There is a need for animal models of CNS diseases and disorders by transplanting neurons into the brains of such animals to produce conditions which resemble or mimic CNS diseases, conditions or disorders.
There is a need for a method of treating individuals suspected of suffering from CNS diseases, conditions or disorders by transplanting neurons in order to replace or introduce cells whose presence reverses or impedes the pathology associated with the disease being treated.
There is a need for a method of treating individuals suspected of suffering from neuron damage caused by stroke or injury such as head trauma, nerve injury or spinal injury by transplanting neurons in order to replace cells damaged by stroke or an injury.